Department of Experimental Clinical Oncology, Aarhus University Hospital, Denmark.
Gustave-Roussy, Paris-Saclay University, Biostatistics and Epidemiology Department, Villejuif, France; INSERM U1018, CESP, Université Paris-Sud, Université Paris-Saclay, Villejuif, France.
Radiother Oncol. 2018 Jan;126(1):107-115. doi: 10.1016/j.radonc.2017.10.018.
Evaluate the prognostic and predictive impact of HPV-associated p16-expression and assess the combined prognostic impact of p16 and smoking on altered fractionated radiotherapy (AFRT) for oropharyngeal cancer (OPC) within the frames of the update of the Meta-Analysis of Radiotherapy in Carcinomas of Head and neck (MARCH).
Patients with OPC, known tumor p16-status and smoking history were identified from the MARCH update, resulting in a dataset of 815 patients from four randomized trials (RTOG9003, DAHANCA6&7, RTOG0129, ARTSCAN). Analysis was performed using a Cox model stratified by trial and adjusted on gender, age, T-stage, N-stage, type of radiotherapy fractionation, p16, smoking. Primary endpoint was progression-free survival (PFS).
In total, 465 patients (57%) had p16-positive tumors and 350 (43%) p16-negative. Compared to p16-negative, p16-positive patients had significantly better PFS (HR = 0.42 [95% CI: 0.34-0.51], 28.9% absolute increase at 10 years) and OS (HR = 0.40 [0.32-0.49], 32.1% absolute increase at 10 years). No interaction between p16-status and fractionation schedule was detected. Smoking negatively impacted outcome; in the p16-positive subgroup, never smokers had significantly better PFS than former/current smokers (HR = 0.49 [0.33-0.75], 24.2% survival benefit at 10 years).
No predictive impact of p16-status on response to AFRT could be detected but the strong prognostic impact of p16-status was confirmed and especially p16-positive never smoking patients have superior outcome after RT.
评估 HPV 相关 p16 表达的预后和预测影响，并在头颈部癌放射治疗荟萃分析（MARCH）更新的框架内，评估 p16 和吸烟对改变分割放疗（AFRT）治疗口咽癌（OPC）的联合预后影响。
从 MARCH 更新中确定了患有 OPC、已知肿瘤 p16 状态和吸烟史的患者，这导致了来自四项随机试验（RTOG9003、DAHANCA6&7、RTOG0129、ARTSCAN）的 815 名患者数据集。使用 Cox 模型进行分析，该模型按试验分层，并根据性别、年龄、T 期、N 期、放疗分割类型、p16、吸烟进行调整。主要终点是无进展生存期（PFS）。
总共 465 名患者（57%）的肿瘤 p16 阳性，350 名患者（43%）的肿瘤 p16 阴性。与 p16 阴性相比，p16 阳性患者的 PFS 明显更好（HR=0.42[95%CI：0.34-0.51]，10 年时绝对增加 28.9%）和 OS（HR=0.40[0.32-0.49]，10 年时绝对增加 32.1%）。未检测到 p16 状态和分割方案之间的相互作用。吸烟对结局有负面影响；在 p16 阳性亚组中，从不吸烟者的 PFS 明显优于前/现吸烟者（HR=0.49[0.33-0.75]，10 年时生存获益 24.2%）。
未检测到 p16 状态对 AFRT 反应的预测影响，但证实了 p16 状态的强烈预后影响，特别是 p16 阳性从不吸烟的患者在接受 RT 后具有更好的结局。
